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A. Korlimbinis, L. Baxter, S. Yun, J. Dahlstrom, M. Koina, R.-A. Sterling, E. Bean, S. Hughes, T. Chan-Ling; Stem Cells Play a Key Role in the Formation of the Human Choroidal Vasculature and Mural Cells. Invest. Ophthalmol. Vis. Sci. 2009;50(13):4939.
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© ARVO (1962-2015); The Authors (2016-present)
To undertake the first complete study of human choroidal vascular formation & determine the role played by stem cells.
Human foetal eyes aged 8-40 weeks gestation (WG) were examined. Choroidal & retinal wholemounts & histological sections were examined using antibodies for stem & precursor cell populations: Vimentin, CD14, CD34, CD39 & SMA; the vasculature: CD39, CD34, CD31 & Factor VIII; & mural cells: SMA, Desmin, NG2, Calponin & Caldesmon. Endothelial proliferation was examined by double-labelling with BrdU & CD34. TEM and H & E histology was also undertaken.
Vimentin+ mesenchymal precursor cells were evident in the region of the incipient choroid at 9 WG, & down regulation of Vimentin was evident with maturation. CD14+ vascular precursor cells (VPCs) were evident in the choroidal stroma throughout foetal life. CD39+/CD34+ VPCs were evident within the choroidal stroma from 10 WG, interspersed amongst CD39+ solid vascular chords in the central one-third of the choroid surrounding the optic nerve head. SMA+ mural precursor cells (MPCs) were scattered & isolated over the primordial vascular tree at 12WG. Non vascular-associated SMA+/CD34+/--/ NG2+/desmin- presumed MPCs were associated with immature choroidal blood vessels at 12, 18 & 20 WG. Calponin & caldesmon were expressed only on the large vessels. Remarkably, pericytes were absent on human choroidal vessels.
We conclude that formation of the human choroid takes place via transformation from Vimentin+ mesenchymal precursor cells to CD14+/CD39+/SMA+ precursor cells representing the monocytic vascular and mural cell lineages respectively. Vasculogenesis plays a greater role in formation of human choroid than previously reported but angiogenesis also contribute to vascular density in the formation of the human choroid. We have shown that CD44+ stem cells give rise to SMA+ smooth muscle cells & CD39+ vascular endothelial cells in the human choroid. Moreover, there is a marked difference in pericyte ensheathment between choroidal & retinal vessels, underlying the marked difference in auto-regulatory ability reported between the two vascular plexii.
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